Although cholesterol metabolism has been studied extensively in the liver and intestinal tract of humans and experimental animals little attention has been directed to the cholesterol metabolism in the male prostate gland and the female mammary gland in both their normal and pathologic diseased states. The etiology and progression for benign and malignant tumors of these glands still remains largely a mystery. Cholesterol-rich diets have had a significant epidemiological association with the variety of human cancer diseases. Particularly, cancers of the prostate and mammary glands and of the colon have been linked to high-fat “western” diets including the intake of fat of animal origin. Kolonel, et al., 1999, J. Natl. Cancer Inst., 91:414-428; Willett, 1989, Nature, 338:389-394. The mechanisms, however, by which these cancers are initiated and progress, as related to the dietary fat, are poorly understood.
The polyene macrolides and in particular, the aromatic heptaene macrolide, candicidin, have been in clinical use for the treatment of human benign prostatic hyperplasia for many years in several countries. Various other hypocholesterolemic drugs that interfere with cholesterol absorption and resorption in the gastrointestinal tract have also been in clinical use for the same human prostatic disease. Schaffner, 1983, in: “Benign Prostatic Hypertrophy”, Frank Hinman, Jr. ed. Springer-Velag, N.Y., pp. 280-307 reviewed clinical studies with candicidin and other polyene macrolides. Candicidin in long-term rat studies has been shown to inhibit tumor initiation and progression as compared to untreated controls. Haditirto, 1974, Ph. D. Dissertation, Rutgers University. Other inhibitors of cholesterol absorption—resorption include the bile acid sequestering anionic exchange resins such as Cholestyramine® and Colestipol®. These have also been shown to alter the course of prostatic disease in animals and humans. Colestipol® inhibited benign prostatic hypertrophy in hamsters. Wang. et al., 1976, Investigative Urol. 14:66-71. Cholestyramine® has been shown to be effective in some patients with prostatic carcinoma. Addleman, 1972, N. England J. Med., 287:1047. As hypocholesterolemic drugs, the phytosterols, beta-sitosterol and stigmasterol, for example, are also known for their ability to inhibit cholesterol absorption and resorption by a mass action effect requiring large doses. In a controlled double blind study beta-sitosterol was found to be effective in the treatment of benign prostatic hyperplasia. Ebbinghaus et al., 1977, Z. Allg. Med., 53:1054-1058. It has been approved for human use in Europe. The phytosterols are also components of a variety of herbal medicines prescribed for the treatment of prostate disease. Extracts of the berries of the plant, saw palmetto, and the bark of Pygeum africanum, also known as Tadenan, for example, contain significant quantities of beta-sitosterol.